This application addresses broad Challenge Area (07): Enhancing Clinical Trials, and specific Challenge Topic, 07-OD(ORDR)-101* Library of Standardized Patient Registry Questions. The primary objective of this application is to develop standardized questions for patient registries across many different rare diseases, which can be used for developing new registries and revising existing ones. The library questions will use consistent structure and language, and the underlying data elements (i.e., questions + answers + definitions) will be encoded using data standards that will facilitate reliable and consistent data collection and enhance opportunities for question re-use and data sharing. In this project, a combination of domain experts in rare diseases research and technical experts will be used to develop a coded library of standardized questions relevant to various rare diseases, with plans for implementation into the broader rare diseases research community. The consistent use of structural and design features across questions and the use of data standards are strong themes in this application, as is the use of flexible and scalable technologies that will support interoperability between various rare diseases. Because we are leveraging existing infrastructures for rare disease research, adapting existing tools for developing libraries of questions, and transport formats that support immediate implementation, we will complete the following within the two-year funding period: develop a library of standardized questions representing 5-10 rare diseases, implement several demonstrations of the library items (i.e., create new registry and extend existing registry), develop implementation materials and resources for users to creating new standardized registry forms, and develop policy and assistance for access to the questions library and supporting tools for a broader rare disease research community.